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A. G. Moore

Updates on Lupus Nephritis Treatment

I recently came across a question about Rituximab on another online forum (Lupus UK) and was curious about this medication. So I began to investigate. As is usual with me, I went down many paths. None of these led to a productive discussion on Rituximab. However, I did learn a lot about lupus nephritis. Below is summarized (from my own blog) some of the most recent thinking about treating this quite common and very serious aspect of systemic lupus--up to 60% of people diagnosed with systemic lupus will eventually be treated for nephritis

The most important thing I can say about lupus nephritis is that the conversation continues: every year more is learned about this manifestation of lupus and every year treatment protocols are fine-tuned.
In 2012, for the first time in 13 years, the American College of Rheumatology revised its treatment guidelines for lupus nephritis (see :http://www.rheumatology.org/practice...Manuscript.pdf ). Some highlights of these new guidelines are:

Biopsies are recommended for anyone with active lupus nephritis who is contemplating treatment for the first time

Depending on the results of the biopsy (how tissue looks upon laboratory examination) patients will be classified into six categories (I through VI, with I being the mildest and VI being the most severe)
introduction of immunosuppressive agents (mycophenolate or cyclophosphamide) in addition to glucocorticoids should be considered for those patients diagnosed with category III lupus nephritis and above.

In most cases mycophenolate and cyclophosphamide appear to be equally effective--however, African Americans seem to have a better response to mycophenolate so this drug might be considered as the treatment of choice for these patients

Hydroxyquinoline should be used as "background" drug for all patients with lupus nephritis.

One interesting fact that is emerging from studies is that a patient's ethnic or economic background may influence the course of lupus nephritis. According to the ACR, for example, people of Asian descent seem to experience a milder course of illness than do Caucasians. In the U. S., African Americans and Hispanics seem to experience a more severe course of illness than Caucasians. Because of this disparity in disease expression, the ACR suggests that in some cases lower doses of immunosuppressive drugs (mycophenolate or cyclophosphamide) may be considered for those populations that tend to have a less severe course of disease. Of course, the ACR panel emphasizes that each physician must apply the information on a case by case basis. Individual responses vary and the physician is in the best position to evaluate the efficacy of a treatment.

Although the ACR is the authority to which rheumatologists look for guidance in deciding on treatment options, it is interesting to note that there is other research which offers some different perspectives on lupus nephritis treatment.

For example, in a paper published by Dr. Gerald Appel, Director of Clinical Nephrology at Columbia Presbyterian Hospital in New York (http://www.ccjm.org/content/79/2/134.long), the effectiveness of mycophenolate and cyclophosphamide are examined for efficacy in the treatment of severe lupus nephritis. Dr. Appel makes some interesting points which do not exactly match those of the ACR. Dr. Appel does conclude that mycophenolate and cyclophoshamide are equally effective; however, he draws attention to one aspect of clinical practice that the ACR does not. Dr. Appel sees the influence of income and social strata as significant actors in the success of a treatment plan. He describes studies which show it is not so much race, as income, that determines the disparity between groups of lupus patients, and he states that a physician should consider this aspect of a patient's background.

Also, since mycophenolate and cyclophosphamide are presumed to be equally efficacious in treating lupus nephritis, he suggests the physician might consider mycophenolate as the preferred medicine because it generally has less severe side effects (such as life-threatening infections and permanent infertility).
While it is Dr. Appel's opinion that mycophenolate be preferred over cyclophosphamides for treatment of severe lupus nephritis, an article published in the Journal of the American Society of Nephrology offers a different perspective. The authors of this article (http://www.ncbi.nlm.nih.gov/pubmed/22879439) state that though mycophenolate and cyclophosphamide are equally effective in inducing remission of severe lupus nephritis, long-term results are better for cyclophosphamide. These researchers analyzed data from a number of studies and extrapolated information. From this it seemed to them that relapse rates and development of end stage renal disease was higher in the group of patient who had taken mycophenolate.

So---what is the patient to think about all of this? If the researchers aren't sure, how can the patient be certain? The answer to that is, there never is certainty. Medicine is an evolving science and its application in a clinical setting is an art. The best a patient can do is be informed. The more informed you are, the more pertinent will be the questions you ask your doctor. If you know what the latest studies say and your doctor doesn't seem to be hooked into that kind of research, then maybe you should look elsewhere for treatment. Your doctor might be a fine person, but you need the best and the brightest on your side when facing an opponent as formidable as lupus nephritis.

Also, when you have determined that your doctor is conversant with the latest research, then you can discuss concerns you might have. What aspects of your treatment plan are important to you (besides driving nephritis into remission)? Are fertility issues paramount? Are you concerned about overwhelming infection?
You may not understand everything the doctor says and you may not be able to make decisions for yourself. But I think, if you understand why you are being treated in a certain way, why a certain side effect is occurring, then you will have a greater sense of control over your life. And I think that is important for everyone.

Please note: I recommend anyone with lupus nephritis read all of the sources referenced in this essay. However, I found Dr. Appel's piece to be the most readable.